Macrocyclic triene lactones having unconjugated triene structure, its production method and its synthetic intermediate

ABSTRACT

The present invention provides a novel macrocyclic compound exhibiting superior odor qualities and having a musk-like aroma, a method for producing the same, and a novel flavor or fragrance composition, and food products or beverages, fragrances or cosmetics, daily necessities or household goods and oral products using the novel macrocyclic compound. The invention relates to a compound represented by the formula (1), wherein each of wavy lines represents at least one of an E-configuration of C═C double bond and an Z-configuration of C═C double bond; m represents an integer of 0 to 10; and n represents an integer of 1 to 11, and n represents an integer of 1 to 11 when m is 0 to 4 or 6 to 10, and n is an integer of 1 or 3 to 11 when m is 5.

TECHNICAL FIELD

The present invention relates to a novel macrocyclic triene lactonecompounds having an unconjugated triene structure commonly found innature, a method for producing the same and the synthetic intermediate.More specifically, the present invention relates to a macrocyclic trienelactone compounds having a musk-like aroma, a method for producing thesame and the synthetic intermediate. Furthermore, the present inventionrelates to a flavor or fragrance composition containing a macrocyclictriene lactone compound(s), and products such as food products orbeverages, fragrances or cosmetics, daily necessities or household goodsand oral products, which contain the compound(s) or the flavor orfragrance composition.

BACKGROUND ART

Natural musk aromas have been considered to be valued as expensiveflavor or fragrances. However, animal-derived musk aromas are not easilyavailable in terms of animal protection and plant-derived musk aromasare difficult to be stably supplied since they readily depend on weatheror the like. Accordingly, synthetic compounds having a musk aroma are ofa great importance. Examples of nature-derived macrocyclic lactoneshaving a musk aroma known to date include Exaltolide found inArchangelica root oils and Ambrettolide found in Ambrette seed oils. Inaddition, examples of synthetic products of macrocyclic lactones includeCyclohexadecanolide and Cyclopentadecenolide (Habanolide) and the like.

Known synthesis methods of macrocyclic monoene lactones includingAmbrettolide include a synthesis method using an intramolecular Wittigreaction (Non-patent Literature 1), a synthesis method starting fromthreo-Aleuritic acid (Non-patent Literature 2), a synthetic method usingan olefin metathesis reaction (Non-patent Literature 3), and a syntheticmethod for 9E-isoambrettolide (Patent Literature 1) and the like. Inaddition, known synthetic methods of macrocyclic diene lactones includea synthetic method for 2E,8E-11-methylcycloundecadien-11-olide using anintramolecular Wittig reaction (Non-patent Literature 1), and asynthetic method using olefin metathesis reaction (Patent Literature 2).2E,10E,12E-Cycloheptadecatrien-17-olide was reported as a macrocyclictriene lactone (Non-patent Literature 4).

In addition, Patent Literature 3 discloses13-hydroxy-5,8,11-tridecatriynoic acid methyl ester (the formula M6below) as ω-hydroxytriyne esters.

Patent Literature 4 discloses 14-hydroxy-5,8,11-tetradecatriynoic acidmethyl ester (the formula 5 below) as ω-hydroxytriyne esters. Inaddition, Patent Literature 4 discloses14-hydroxy-5,8,11-tetradecatrienoic acid methyl ester (the formula 6below) as ω-hydroxytriene esters.

CITATION LIST Patent Literature

-   [PTL 1] U.S. Pat. No. 3,681,395-   [PTL 2] WO 2009/039675-   [PTL 3] JP-A-2008-515978-   [PTL 4] US Patent Application Publication No. 2004/122089

Non-Patent Literature

-   [NPL 1] Synthesis (1989), p. 419-423-   [NPL 2] Synthesis (1987), p. 154-155-   [NPL 3] Lecture Abstract of 51^(th) Symposium on flavor or    fragrance/terpenes and essential oil chemicals, p. 199-201-   [NPL 4] Asian Journal of chemistry (2005), p. 859-870

SUMMARY OF INVENTION Technical Problem

As mentioned above, various macrocyclic lactones or synthesis thereofwere reported. However, macrocyclic lactones having an unconjugatedtriene structure and/or a synthetic method thereof are not known.

In addition, usefulness of compounds disclosed in Patent Literature 3and Patent Literature 4 as intermediates for the preparation of flavoror fragrance compounds is not disclosed.

Accordingly, an aspect of the present invention is to provide a novelmacrocyclic compound that satisfies these requirements, exhibitsexcellent odor quality and has a unique musk-like aroma, and a methodfor producing the same. Another aspect of the present invention is toprovide a flavor or fragrance composition containing the macrocycliccompound having these characteristics. Yet another aspect of the presentinvention is to provide products such as food products or beverages,fragrances or cosmetics, daily necessities or household goods and oralproducts, which contain the compound or the flavor or fragrancecomposition.

Solution to Problem

As a result of intensive studies to solve the above-mentioned problems,the present inventors have intensive studies and found that macrocyclictriene lactones having an unconjugated triene structure commonly foundin nature represented by the formula (1) has a unique musk aroma.

That is, the invention encompasses the following embodiments.

[1] A compound represented by the following formula (1):

wherein each of wavy lines represents at least one of an E-configurationof C═C double bond and an Z-configuration of C═C double bond; mrepresents an integer of 0 to 10; and n represents an integer of 1 to11, wherein n represents an integer of 1 to 11 when m is 0 to 4 or 6 to10; and n is an integer of 1 or 3 to 11 when m is 5.

[2] The compound according to [1], wherein all of the wavy lines are theZ-configuration of C═C double bond.

[3] The compound according to [1] or [2], which has a musk aroma.

[4] A method for producing a compound represented by the followingformula (1),

wherein each of wavy lines represents at least one of an E-configurationof C═C double bond and an Z-configuration of C═C double bond; mrepresents an integer of 0 to 10; and n represents an integer of 1 to11,

which comprises:

hydrogenating an ω-hydroxytriyne esters represented by the followingformula (2):

wherein m represents an integer of 0 to 10; n represents an integer of 1to 11; and R represents a monovalent aromatic ring group having 6 to 20carbon atoms, or a monovalent hydrocarbon group having 1 to 20 carbonatoms which may have a substituent group;

and lactonizing an ω-hydroxytriene esters represented by the followingformula (3) obtained by the hydrogenation:

wherein m represents an integer of 0 to 10; n represents an integer of 1to 11; and R represents a monovalent aromatic ring group having 6 to 20carbon atoms, or a monovalent hydrocarbon group having 1 to 20 carbonatoms which may have a substituent group, and each of wavy linesrepresents at least one of an E-configuration of C═C double bond and anZ-configuration of C═C double bond.

[5] The method according to [4], wherein all of the wavy lines in theformula (1) are the Z-configuration of C═C double bond.

[6] The method according to [4] or [5], wherein the compound representedby the formula (1) in which all of the wavy lines are theZ-configuration of C═C double bond is produced in a ratio of 95% or morebased on the whole of the produced compounds represented by the formula(1), and the rest can either be geometrical isomers.

[7] The method according to any one of [4] to [6], wherein thew-hydroxytriene esters represented by the formula (3) is lactonized withtitanate.

[8] A ω-hydroxytriyne esters represented by the following formula (2):

wherein m represents an integer of 0 to 10; n represents an integer of 1to 11; and R represents a monovalent aromatic ring group having 6 to 20carbon atoms, or a monovalent hydrocarbon group having 1 to 20 carbonatoms which may have a substituent group, and a compound in which m is3, n is 1 and R is a methyl group and a compound in which m is 3, n is 2and R is a methyl group are excluded.

[9] A ω-hydroxytriene esters represented by the following formula (3):

wherein m represents an integer of 0 to 10; n represents an integer of 1to 11; and R represents a monovalent aromatic ring group having 6 to 20carbon atoms, or a monovalent hydrocarbon group having 1 to 20 carbonatoms which may have a substituent group, and a compound in which m is3, n is 2 and R is a methyl group is excluded, and each of wavy linesrepresents at least one of an E-configuration of C═C double bond and anZ-configuration of C═C double bond.

[10] The ω-hydroxytriene esters according to [9], wherein all of thewavy lines are the Z-configuration of C═C double bond.

[11] A flavor or fragrance composition comprising the compound accordingto any one of [1] to [3].

[12] A product comprising the compound according to any one of [1] to[3], wherein the product is selected from the group consisting of a foodproduct or beverage, a fragrance or cosmetic, a daily necessities andhousehold goods and an oral product.

[13] A product comprising the flavor or fragnrace composition accordingto [11], wherein the product is selected from the group consisting of afood product or beverage, a fragrance or cosmetic, a dialy necessitiesand household goods and an oral product.

Advantageous Effects of Invention

The compound of the present invention represented by the formula (1),that is, a macrocyclic triene lactone having an unconjugated trienestructure has a musk-like aroma, in particular, unique musk-like aromasuch as fruit-like, floral-like, creamy-like and animal-like.Accordingly, the compound may be effectively used directly, or in theform of a flavor or fragrance composition for a variety of products suchas food products or beverages, fragrances or cosmetics, dailynecessities or household goods and oral products and furthermore, canimpart the desired fragrances and flavors to various products.

Also, according to the production method of the present invention, it ispossible to selectively produce a compound represented by the formula(1) having a particularly excellent odor in which all C═C double bondsare in the Z-configuration among the compounds represented by theformula (1) on an industrial scale and at a high purity.

DESCRIPTION OF EMBODIMENTS

In this specification, “% by weight” and “parts by weight” have the samemeanings as “% by mass” and “parts by mass”, respectively.

Hereinafter, the macrocyclic triene lactone having an unconjugatedtriene structure according to the present invention will be described indetail.

<Compound Represented by the Formula (1)>

The macrocyclic triene lactone having an unconjugated triene structureaccording to the present invention is a compound represented by theformula (1) below.

In the formula (1), each of wavy lines represents at least one ofE-configuration of C═C double bond and a Z-configuration of C═C doublebond. m represents an integer of 0 to 10 and n represents an integer of1 to 11. When m represents an integer of 0 to 4 or 6 to 10, n representsan integer of 1 to 11. In addition, when m is 5, n represents an integerof 1 or 3 to 11.

The compound represented by the formula (1) is preferably a 15-memberedring compound, 16-membered ring compound or 17-membered ring compound.

As the 15-membered ring compound, in particular, compounds representedby the formula (1) satisfying (m=0, n=5), (m=1, n=4), (m=2, n=3), (m=3,n=2) and (m=4, n=1) are preferred.

As the 16-membered ring compound, in particular, compounds representedby the formula (1) satisfying (m=0, n=6), (m=1, n=5), (m=2, n=4), (m=3,n=3), (m=4, n=2) and (m=5, n=1) are preferred.

As the 17-membered ring compound, in particular, compounds representedby the formula (1) satisfying (m=0, n=7), (m=1, n=6), (m=2, n=5), (m=3,n=4), (m=4, n=3), and (m=6, n=1) are preferred.

Specifically, the compounds represented by the formula (1) include:

6,9,12-tetradecatrien-14-olide in which m is 4 and n is 1;

6,9,12-pentadecatrien-15-olide in which m is 4 and n is 2;

7,10,13-pentadecatrien-15-olide in which m is 5 and n is 1;

5,8,11-hexadecatrien-16-olide in which m is 3 and n is 4; and

6,9,12-hexadecatrien-16-olide in which m is 4 and n is 3.

Of these, the compound represented by the formula (1) is preferably acompound in which all three C═C double bonds are in the Z-configurations(hereinafter, a compound in which all C═C double bonds are in theZ-configuration will be referred to as a “Z-form”) in terms of odorquality and diffusion property.

Specifically, examples of the compound include:

(6Z,9Z,12Z)-tetradecatrien-14-olide in which m is 4 and n is 1;

(6Z,9Z,12Z)-pentadecatrien-15-olide in which m is 4 and n is 2;

(7Z,10Z,13Z)-pentadecatrien-15-olide in which m is 5 and n is 1;

(5Z,8Z,11Z)-hexadecatrien-16-olide in which m is 3 and n is 4; and

(6Z,9Z,12Z)-hexadecatrien-16-olide in which m is 4 and n is 3.

The compounds represented by the formula (1) generally include, inaddition to a compound (Z-form) in which three C═C double bonds are inthe Z-configuration, a mixture of a compound (E-form) in which three C═Cdouble bonds are in the E-configuration, a compound in which one C═Cdouble bond is in the E-configuration and two C═C double bonds are inthe Z-configuration, and a compound in which one C═C double bond is inthe Z-configuration and two C═C double bonds are in the E-configuration.The mixture in which the ratio of the Z-form is 95% or more ispreferable in terms of odor quality and diffusion property.

These compounds have each unique and attractive musk-like aroma. Theterm “unique and attractive musk-like aroma” refers to a musk aroma suchas fruit-like, floral-like, creamy-like and animal-like aroma.

(Production Method)

Next, a production method of the macrocyclic triene lactone having anunconjugated triene structure represented by the following formula (1)according to the present invention will be described.

In the present invention, the compound represented by the formula (1) isproduced by the method including hydrogenating ω-hydroxytriyne estersrepresented by the formula (2) and lactonizing ω-hydroxytriene estersrepresented by the formula (3) which is obtained by the hydrogenation.

In the formula (2), m represents an integer of 0 to 10, n represents aninteger of 1 to 11, and R represents a monovalent aromatic ring grouphaving 6 to 20 carbon atoms or a monovalent hydrocarbon group having 1to 20 carbon atoms which may have a substituent group.

In the formula (3), m represents an integer of 0 to 10, n represents aninteger of 1 to 11, and R represents a monovalent aromatic ring grouphaving 6 to 20 carbon atoms or a monovalent hydrocarbon group having 1to 20 carbon atoms which may have a substituent group. Each of wavylines represents at least one of an E-configuration of C═C double bondand a Z-configuration of C═C double bond.

In the formula (1), each of wavy lines represents at least one of anE-configuration of C═C double bond and a Z-configuration of C═C doublebond, and m represents an integer of 0 to 10, and n represents aninteger of 1 to 11.

The production method of the compound represented by the formula (1)will be described in detail in accordance with the following Scheme 1.

The following description will be given under the condition that R inthe formula (2) and formula (3) is a methyl group, but the presentinvention is not limited thereto.

<Scheme 1>

Hereinafter, Me represents a methyl group, Et represents an ethyl groupand Ph represents a phenyl group, and m represents an integer of 0 to 10and n represents an integer of 1 to 11.

First, ω-hydroxydiyne ester (III) is obtained by coupling reaction ofchlorohydrin (I) with alkyne carboxylic acid ester (II). Examples of thesolvent used herein include dimethylformamide (hereinafter, alsoreferred to “DMF”), dimethylacetamide, dimethylsulfoxide, acetonitrileand the like. The amount of the solvent used can be decided based ontypical procedure in this inductry. Usual choice could be of 0.1 to 100times content (ml), more preferably 5 to 50 times content based on theweight (g) of chlorohydrin (I) as a substrate (hereinafter, a unit of[solvent ml/substrate g] will be referred to as “time(s) content”). Thereaction temperature is preferably 0 to 100° C., more preferably 20 to50° C. The reaction time is 0.5 to 100 hours, preferably 3 to 60 hours.

As reaction aids, an equimolar or more amount, preferably 1 to 2equivalent of base such as potassium carbonate, sodium carbonate,calcium carbonate and barium carbonate, and iodide such as sodiumiodide, potassium iodide and lithium iodide in an amount of 0.01 to 2equivalents, preferably 1 to 2 equivalents against chlorohydrin (I) canbe used. In addition, copper iodide is used as a reaction catalyst in anamount of 0.01 to 2 equivalents, preferably 0.2 to 1 equivalents basedon chlorohydrin (I).

The obtained ω-hydroxydiyne ester (III) is brominated to obtainbromodiyne ester (IV) and ω-hydroxytriyne esters (2) are obtained bycoupling reaction of the bromodiyne ester with alkyne alcohol (V). Thebromination of ω-hydroxydiyne ester (III) may be carried out usingcarbon tetrabromide and triphenyl phosphine in a dichloromethanesolvent, but the present invention is not limited thereto.

The coupling reaction of the obtained bromodiyne ester (IV) with alkynealcohol (V) may be carried out under the same conditions as couplingreaction of chlorohydrin (I) with alkyne carboxylic acid ester (II). Inaddition, instead of bromodiyne ester (IV), chloride, iodide, mesylateor tosylate can be used.

Next, the ω-hydroxytriyne esters represented by the formula (2) arehydrogenated to obtain ω-hydroxytriene esters represented by the formula(3).

The hydrogenation is preferably carried out in the presence of amineusing nickel boride as a catalyst. As a result, a Z-form thereof can beselectively obtained. Alternatively, a Z-form thereof can be selectivelyobtained using a Lindlar catalyst or the like.

The amount of nickel boride used as a hydrogenation catalyst ispreferably 0.1 to 5 equivalents, more preferably 0.5 to 2 equivalentsbased on ω-hydroxytriyne esters represented by the formula (2).

Examples of amine used for hydrogenation include quinoline, pyridine,piperidine, morpholin, triethylamine, ethylene diamine, 1,2-propylenediamine and the like. In order to improve the selectivity of the Z-form,ethylene diamine is particularly preferably used. The amount of theamine used is preferably 0.1 to 10 equivalents, more preferably 1 to 6equivalents based on ω-hydroxytriyne esters represented by the formula(2).

Examples of the solvent used for hydrogenation include methanol,ethanol, isopropyl alcohol, ethyl acetate, butyl acetate, toluene,xylene, hexane, heptane, cyclohexane and methylcyclohexane and the like.The amount of the solvent used is preferably 3 to 100 times content(ml), more preferably 20 to 70 times content based on the weight (g) ofω-hydroxytriyne esters represented by the formula (2) as a substrate.

The hydrogenation reaction temperature is preferably 0 to 50° C., morepreferably 10 to 40° C. The reaction time is preferably 0.5 to 10 hours.The reaction pressure is preferably atmospheric pressure to 10 atm, morepreferably atmospheric pressure.

Next, the obtained ω-hydroxytriene esters represented by the formula (3)is lactonized to prepare a compound represented by the formula (1) as aZ-form.

For example, the lactonization may be carried out by refluxing thew-hydroxytriene esters in a solvent using a titanate catalyst.

Examples of titanate include titanium (IV) methoxide, titanium (IV)ethoxide, titanium (IV) isopropoxide, titanium (IV) isobutoxide,titanium (IV) t-butoxide, titanium (IV) octadecyloxide and the like. Theamount of titanate used is preferably 0.01 to 10 equivalents, morepreferably 0.1 to 1 equivalents based on ω-hydroxytriene estersrepresented by the formula (3), as a substrate.

Examples of the solvent used for lactonization include benzene, toluene,xylene cyclohexane, methylcyclohexane and the like. The amount of thesolvent used is preferably 1 to 2000 times content, more preferably 200to 1000 times content, based on ω-hydroxytriene esters represented bythe formula (3), as a substrate.

The reaction temperature of the lactonization is preferably 50 to 200°C., more preferably 80 to 150° C. The reaction time is preferably 0.5 to20 hours, more preferably 3 to 10 hours.

In addition, the Z-form compound represented by the formula (1) can beobtained, instead of the lactonization, by polymerization anddepolymerization in which the ω-hydroxytriene esters represented by theformula (3) is heated to prepare an oligomer thereof and the oligomer isheated under reduced pressure to perform depolymerization.

According to the production method, a Z-form compound is selectivelyobtained at a high purity among the compounds represented by the formula(1). In particular, the Z-form can be obtained with the purity of 95% ormore.

Specifically, examples of the compound represented by the formula (1)obtained by the production method include:

(7Z,10Z,13Z)-hexadecatrien-16-olide in which m is 5 and n is 2;

(6Z,9Z,12Z)-tetradecatrien-14-olide in which m is 4 and n is 1;

(6Z,9Z,12Z)-pentadecatrien-15-olide in which m is 4 and n is 2;

(7Z,10Z,13Z)-pentadecatrien-15-olide in which m is 5 and n is 1;

(5Z,8Z,11Z)-hexadecatrien-16-olide in which m is 3 and n is 4; and

(6Z,9Z,12Z)-hexadecatrien-16-olide in which m is 4 and n is 3.

The Z-form compound represented by the formula (1) obtained by theproduction method has a musk aroma, in particular, unique musk aromasuch as fruit-like, floral-like, creamy-like, animal-like.

<Compounds Represented by the Formula (2) and Formula (3)>

Next, the compounds represented by the formula (2) and formula (3)according to the present invention, as intermediates of the productionmethod of the compound represented by the formula (1), will bedescribed.

The ω-hydroxytriyne esters represented by the formula (2) will be givenas follows.

In the formula (2), m represents an integer of 0 to 10, and n representsan integer of 1 to 11. R represents a monovalent aromatic ring grouphaving 6 to 20 carbon atoms, or a monovalent hydrocarbon group having 1to 20 carbon atoms which may have a substituent group.

The ω-hydroxytriene esters represented by the formula (3) will be givenas follows.

In the formula (3), m represents an integer of 0 to 10 and n representsan integer of 1 to 11. R represents a monovalent aromatic ring grouphaving 6 to 20 carbon atoms, or a monovalent hydrocarbon group having 1to 20 carbon atoms which may have a substituent group. Each of wavylines represents at least one of an E-configuration of C═C double bondand a Z-configuration of C═C double bond.

The compound represented by the formula (3) is preferably a compound inwhich all three C═C double bonds are in the Z-configuration, andparticularly preferably, the compound in which three C═C double bondsare Z-configuration is present at 95% or more.

The R in the formulae (2) and (3), which is a monovalent aromatic ringgroup having 6 to 20 carbon atoms or a monovalent hydrocarbon grouphaving 1 to 20 carbon atoms which may have a substituent group, will bedescribed.

Examples of the monovalent aromatic ring group having 6 to 20 carbonatoms include a phenyl group, a tolyl group, a benzyl group, a naphthylgroup and the like. In addition, the number of carbon atoms ispreferably 6 to 10.

Examples of the monovalent hydrocarbon group having 1 to 20 carbon atomswhich may have a substituent group, include a linear or branchedhydrocarbon group and a cyclic hydrocarbon group, and the monovalenthydrocarbon group may contain a carbon-carbon unsaturated bond. Inaddition, the number of carbon atoms is preferably 1 to 12. Examples ofthe monovalent hydrocarbon group include an alkyl group, an alkenylgroup, an alkynyl group, a cycloalkyl group, a cycloalkenyl group andthe like.

Examples of the alkyl group include a methyl group, an ethyl group, ann-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group,a tert-butyl group, an n-pentyl group, an n-hexyl group, an n-heptylgroup, an octyl group, a nonyl group and the like.

Examples of the alkenyl group include a vinyl group, an allyl group, apropenyl group, an isopropenyl group, a 2-methyl-1-propenyl group, amethallyl group, a 2-butenyl group and the like.

Examples of the alkynyl group include an ethynyl group, a propynylgroup, a butynyl group and the like.

Examples of the cycloalkyl group include a cyclobutyl group, acyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctylgroup and the like.

Examples of the cycloalkenyl group include a cyclobutenyl group, acyclopentenyl group, a cyclohexenyl group and the like.

Examples of the substituent that the monovalent hydrocarbon group having1 to 20 carbon atoms may have include a phenyl group, a tolyl group, abenzyl group, a naphthyl group and the like.

In the formula (2) and formula (3), R is preferably a methyl group, anethyl group or the like, but is not limited thereto.

In the formula (2) and formula (3), m is 0 to 10 and n is 1 to 11.

Compounds that satisfying (m=0, n=5), (m=1, n=4), (m=2, n=3), (m=3,n=2), or (m=4, n=1) in the formula (2) and formula (3) are preferred asintermediates of 15-membered ring compounds represented by the formula(1).

Compounds that satisfying (m=0, n=6), (m=1, n=5), (m=2, n=4), (m=3,n=3), (m=4, n=2), or (m=5, n=1) in the formula (2) and formula (3) arepreferred as intermediates of 16-membered ring compounds represented bythe formula (1).

Compounds that satisfying (m=0, n=7), (m=1, n=6), (m=2, n=5), (m=3,n=4), (m=4, n=3), (m=5, n=2), or (m=6, n=1) in the formula (2) andformula (3) are preferred as intermediates of 17-membered ring compoundsrepresented by the formula (1).

Specifically, the compounds represented by the formula (2) include:

methyl 16-hydroxyhexadeca-7,10,13-triynoate in which m is 5, n is 2 andR is methyl;

methyl 14-hydroxytetradeca-6,9,12-triynoate in which m is 4, n is 1 andR is methyl;

methyl 15-hydroxypentadeca-6,9,12-triynoate in which m is 4, n is 2 andR is methyl;

methyl 15-hydroxypentadeca-7,10,13-triynoate in which m is 5, n is 1 andR is methyl;

methyl 16-hydroxyhexadeca-5,8,11-triynoate in which m is 3, n is 4 and Ris methyl; and

methyl 16-hydroxyhexadeca-6,9,12-triynoate in which m is 4, n is 3 and Ris methyl.

Specifically, the compounds represented by the formula (3) include:

methyl 16-hydroxyhexadeca-(7Z,10Z,13Z)-trienoate in which m is 5, n is 2and R is methyl;

methyl 14-hydroxytetradeca-(6Z,9Z,12Z)-trienoate in which m is 4, n is 1and R is methyl;

methyl 15-hydroxypentadeca-(6Z,9Z,12Z)-trienoate in which m is 4, n is 2and R is methyl;

methyl 15-hydroxypentadeca-(7Z,10Z,13Z)-trienoate in which m is 5, n is1 and R is methyl;

methyl 16-hydroxyhexadeca-(5Z,8Z,11Z)-trienoate in which m is 3, n is 4and R is methyl; and

methyl 16-hydroxyhexadeca-(6Z,9Z,12Z)-trienoate, in which m is 4, n is 3and R is methyl.

The compounds represented by the formula (2) and formula (3) are usefulas intermediates for producing the compound represented by the formula(1).

In addition, all compounds excluding the compound represented by theformula (2) in which m is 3, n is 1 and R is a methyl group andcompounds represented by the formulae (2) and (3) in which m is 3, n is2 and R is a methyl group are novel compounds.

(Food Products or Beverages, Fragrances or Cosmetics, Daily Necessitiesand Household Goods, and Oral Products)

The compound of the present invention represented by the formula (1) canbe used as a flavor or fragrance compound for imparting fragrance orflavor to various products such as food products or beverages,fragrances or cosmetics, daily necessities and household goods, and oralproducts.

As the food products or beverages to which the flavor is imparted by thecompound of the present invention represented by the formula (1),examples thereof include drinks such as fruit juice drinks, fruit wines,milk drinks, carbonated drink, soft drink and drink preparations; frozensweets such as ice creams, sherbets and ice candies; desserts such asjelly and pudding; Western style confections such as cake, cookie,chocolate and chewing gum; Japanese style confections such as bean-jambun, sweet beans jelly and Uiro; jams; candies; breads; tea drinks orluxury drinks such as green tea, Oolong tea, black tea, persimmon leaftea, chamomile tea, low striped bamboo tea, mulberry tea, Dokudami tea,Pu-erh tea, Mate tea, Rooibos tea, Gymnema tea, Guava tea, coffee andcocoa; soups such as Japanese style soup, Western style soup and Chinesesoup; flavoring and seasoning; various instant drinks or conveniencefoods; various snack foods and the like.

As the fragrances or cosmetics to which the fragrance is imparted by thecompound of the present invention represented by the formula (1),examples thereof include fragrance products, foundation cosmetics,finishing cosmetics, hair cosmetics, sun care cosmetics, medicatedcosmetics and the like.

More illustratively, examples thereof include,

as the fragrance products, perfume, eau de perfume, eau de toilette, eaude cologne and the like;

as the foundation cosmetics, facial cleansing cream, banishing cream,cleansing cream, cold cream, massage cream, milky lotion, skin lotion,beauty lotion, pack, makeup remover and the like;

as the finishing cosmetics, foundation, face powder, solid face powder,talcum powder, rouge, lip barm, lip cream, cheek rouge, eye liner,mascara, eye shadow, eyebrow pencil, eye pack, nail enamel, enamelremover and the like;

as the hair cosmetics, pomade, brilliantine, set lotion, hair stick,hair solid, hair oil, hair treatment, hair cream, hair tonic, hairliquid, hair spray, bandrine, revitalizing hair tonic, hair dye and thelike;

as the sun care cosmetics, suntan products, sunscreen product and thelike; and

as the medicated cosmetics, antiperspirant, after shaving lotion, gel,permanent wave agent, medicated soap, medicated shampoo, medicated skincosmetics and the like.

As the dialy necessities and household goods to which the fragrance orflavor is imparted by the compound of the present invention representedby the formula (1), examples thereof include hair care products, soap,body washers, bath agents, cleansers, soft finishing agents, detergents,kitchen cleaners, bleachers, aerosols, deodorants or aromatics,household goods, shaving products, skin care products, repellents,cigarette products, and the like.

More illustratively, examples thereof include,

as the hair care products, shampoo, rinse, rinse-in-shampoo,conditioner, treatment, hair pack and the like;

as the soap, toilet soap, bath soap, perfume soap, transparent soap,synthetic soap and the like;

as the body washers, body soap, body shampoo, hand soap and the like;

as the bath agents, bathing agents (bath salt, bath tablet, bath liquidand the like), foam bath (bubble bath and the like), bath oil (bathperfume, bath capsule and the like), milk bath, bath jelly, bath cubeand the like;

as the detergents, heavy detergent for clothing use, light detergent forclothing use, liquid detergent, washing soap, compact detergent, powdersoap and the like;

as the soft finishing agents, softener, furniture care and the like;

as the cleaners, cleanser, house cleaner, toilet cleaner, bath cleaner,glass cleaner, mildew remover, cleaner for drainpipe use and the like;

as the kitchen cleaners, kitchen soap, kitchen synthetic soap, tablewarecleaner and the like;

as the bleachers, oxidation type bleacher (chlorine type bleacher,oxygen type bleacher and the like), reduction type bleacher (sulfur typebleacher and the like), optical bleacher and the like;

as the aerosols, spray type, powder spray and the like;

as the deodorants or aromatics, solid type, gel type, liquid type andthe like;

as the household goods, tissue paper, toilet paper and the like;

as the shaving products, shaving foams and the like; and

as the skin care products, hand cream, body cream, body lotion and thelike.

Examples of the oral products to which the fragrance or flavor isimparted by the compound of the present invention represented by theformula (1) include toothpaste, mouth cleansing agents, mouthwashes,troche, chewing gums and the like.

The content of the compound of the present invention represented by theformula (1) in the food products or beverages is preferably 1×10⁻¹° to0.01% by weight, more preferably 1×10⁻⁷ to 0.001% by weight based on thetotal weight of the food products or beverages.

The content of the compound of the present invention represented by theformula (1) in the fragrances or cosmetics is preferably 0.00001 to 0.3%by weight, more preferably 0.001 to 0.05% by weight by weight based onthe total weight of the fragrances or cosmetics.

The content of the compound of the present invention represented by theformula (1) in the daily necessities and household goods is preferably0.00001 to 0.3% by weight, more preferably 0.001 to 0.05% by weightbased on the total weight of the daily necessities and household goods.

The content of the compound of the present invention represented by theformula (1) in the oral product is preferably 1×10⁻⁷ to 0.001% byweight, more preferably 1×10⁻⁵ to 0.0001% by weight based on the totalweight of the oral product.

<Flavor or Fragrance Composition>

The compound of the present invention represented by the formula (1) mayconstitute a flavor or fragrance composition together with other flavoror fragrance components.

Examples of other flavor or fragrance component that can be contained inthe flavor or fragrance composition in conjunction with the compound ofthe present invention represented by the formula (1) include syntheticaromachemicals; materials of natural origine such as essential oils,oleoresin, extracts, animal aromachemicals, and the like.

Any synthetic aromachemicals may be used for the flavor or fragrancecomposition of the present invention without particular limitation solong as it has been used in the related art to impart fragrances andflavors. Examples of synthetic aromachemicals include flavor orfragrance components disclosed in “Synthetic aromachemical: Chemistryand Product Knowledge” (published on Mar. 6, 1996, written by MotoichiIndo, The Chemical Daily Co., Ltd.), and “Perfume and Flavor Chemicals(Aroma Chemicals) 1, 2” (Steffen Arctender (1969)).

As the synthetic aromachemical, examples thereof include at least oneselected from the group consisting of esters, alcohols, aldehydes,ketones, phenols, ethers, lactones, hydrocarbons, nitrogen-containingcompounds, sulfur-containing compounds and acids.

Examples of the esters include propyl formate, butyl formate, amylformate, octyl formate, linalyl formate, citronellyl formate, geranylformate, neryl formate, terpinyl formate, ethyl acetate, isopropylacetate, isoamyl acetate, hexyl acetate, cis-3-hexenyl acetate,trans-2-hexenyl acetate, octyl acetate, nonyl acetate, decyl acetate,dodecyl acetate, dimethylundecadienyl acetate, styrallyl acetate,ocimenyl acetate, myrcenyl acetate, dihydromyrcenyl acetate, linalylacetate, citronellyl acetate, geranyl acetate, neryl acetate, acetate oftetrahydromugol, lavandulyl acetate, nerolidyl acetate, dihydrocuminylacetate, terpinyl acetate, citryl acetate, nopyl acetate,dihydroterpinyl acetate, 2,4-dimethyl-3-cyclohexenylmethyl acetate,miraldyl acetate, veticol acetate, decenyl propionate, linalylpropionate, geranyl propionate, neryl propionate, terpinyl propionate,tricyclodecenyl propionate, styrallyl propionate, anisyl propionate,octyl butyrate, neryl butyrate, cinnamyl butyrate, isopropylisobutyrate, octyl isobutyrate, linalyl isobutyrate, neryl isobutyrate,linalyl isovalerate, terpinyl isovalerate, phenylethyl isovalerate,2-methyl-2-methylpentyl valerate, methyl 3-hydroxyhexanoate, ethyl3-hydroxyhexanoate, methyl octanoate, octyl octanoate, linalyloctanoate, methyl nonanoate, methyl undecylenate, linalyl benzoate,methyl cinnamate, isoprenyl angelicate, methyl gallate, triethylcitrate, ethyl acetoacetate, ethyl 2-hexylacetoacetate, ethyl benzylacetoacetate, allyl 2-ethylbutyrate, ethyl 3-hydroxybutyrate, ethylnonanoate, ethyl decanoate, ethyl 2,4-decadienoate, propyl2,4-decadienoate, methyl anthranilate and linalyl anthranilate, ethylN-methylanthranilate and the like.

Examples of the alcohols include 3-heptanol, 1-nonanol, 1-undecanol,2-undecanol, 1-dodecanol, prenol, 10-undecen-1-ol, dihydrolinalool,tetrahydromugol, myrcenol, dihydromyrcenol, tetrahydromyrcenol,ocimenol, terpineol, hotrienol, 3-thujanol, benzyl alcohol,β-phenylethylalcohol, α-phenylethylalcohol, 3-methyl-1-pentanol,1-heptanol, 2-heptanol, 3-octanol, 1-nonanol, 2-nonanol,2,6-dimethylheptanol, 1-decanol, trans-2-hexenol, cis-4-hexenol,methyl-trimethylcyclopentenylbutenol, citronellol, dihydromyrcenol,rhodinol, geraniol, nerol, linalool, tetrahydrolinalool,dimethyloctanol, hydroxycitronellol, isopulegol, menthol, terpineol,dihydroterpineol, carveol, dihydrocarveol, perilla alcohol, 4-thujanol,myrtenol, α-fenchyl alcohol, farnesol, nerolidol, cedrenol, Anisealcohol, hydratropic alcohol, 3-phenylpropyl alcohol, cinnamic alcohol,amylcinnamic alcohol and the like.

Examples of the aldehydes include acetaldehyde, n-hexanal, n-heptanal,n-octanal, n-nonanal, 2-methyloctanal, 3,5,5-trimethylhexanal, decanal,undecanal, 2-methyldecanal, dodecanal, tridecanal, tetradecanal,trans-2-hexenal, trans-4-decenal, cis-4-decenal, trans-2-decenal,10-undecenal, trans-2-undecenal, trans-2-dodecenal, 3-dodecenal,trans-2-tridecenal, 2,4-hexadienal, 2,4-decadienal, 2,4-dodecadienal,5,9-dimethyl-4,8-decadienal, citral, dimethyloctanal, α-methylenecitronellal, citronellyloxyacetaldehyde, myrtenal, neral, α- orβ-cinensal, myrac aldehyde, phenylacetaldehyde, octanal dimethyl acetal,nonanal dimethyl acetal, decanal dimethyl acetal, decanal diethylacetal, 2-methylundecanal dimethyl acetal, citral dimethyl acetal,citral diethyl acetal, citral propylene glycol acetal, n-valeraldehyde,isovaleraldehyde, 2-methylbutanal, 2-pentenal, trans-2-heptenal,trans-2-nonenal, 2,6-dimethyl-5-heptenal, 2,4-undedienal,trimethyldecadienal, citronellal, hydroxycitronellal, safranal,Vernaldehyde, benzaldehyde, p-isopropylphenylacetaldehyde,p-methylhydrotropaldehyde, phenylpropionaldehyde,2-methyl-3-(4-methylphenyl)propanal, cyclamen aldehyde, cinnamicaldehyde, salicylic aldehyde, anisaldehyde, p-methylphenoxyacetaldehyde,acetaldehydediethylacetal, citronellylmethylacetal,acetaldehyde-2-phenyl-2,4-pentanediol acetal, 2-hexenaldiethylacetal,cis-3-hexenal diethyl acetal, heptanal diethyl acetal,2-hexyl-5-methyl-1,3-dioxolane, citronellal cyclomonoglycol acetal,hydroxyl citronellal dimethyl acetal, phenylacetaldehyde dimethyl acetaland the like.

Examples of the ketones include 2-pentanone, 3-hexanone, 2-heptanone,3-heptanone, 4-heptanone, 2-octanone, 3-octanone, 2-nonanone,2-undecanone, methylheptenone, dimethyl octenone, geranyl acetone,farnesyl acetone, 2,3,5-trimethyl-4-cyclohexenyl-1-methylketone, nerone,nootkatone, dihydronootkatone, acetophenone,4,7-dihydro-2-isopentyl-2-methyl-1,3-dioxepine, 2,3-hexadione,3-nonanone, ethylisoamylketone, diacetyl, amylcyclopentenone,2-cyclopentylcyclopentanone, hexylcyclopentanone, heptylcyclopentanone,cis-jasmone, dihydrojasmone, trimethylpentylcyclopentanone,2-(2-(4-methyl)-3-cyclohexen-1-yl)propyl cyclopentanone, damascone,α-dynascone, trimethylcyclohexenylbutenone, ionone, methylionone,allylionone, plicatone, cashmeran, l-carvone, menthone, camphor,p-methylacetophenone, p-methoxyacetophenone, benzylidene acetone,raspberry ketone, methylnaphthyl ketone, benzophenone, furfural acetone,homofuronol, maltol, ethyl maltol, ethylacetoacetate ethyleneglycolketal and the like.

Examples of the phenols include thymol, carvacrol,β-naphtholisobutylether, anethole, β-naphtholmethylether,β-naphtholethylether, creosol, veratrole, hydroquinonedimethylether,2,6-dimethoxyphenol, 4-ethylguaiacol, eugenol, isoeugenol,ethylisoeugenol, tert-butylhydroquinonedimethylether and the like.

Examples of the ethers include decylvinylether, α-terpenylmethylether,isoproxen, 2,2-dimethyl-5-(1-methyl-1-propenyl)-tetrahydrofuran,rosefuran, 1,4-cineol, nerol oxide,2,2,6-trimethyl-6-vinyltetrahydropyran, methylhexylether, ocimeneepoxide, limonene oxide, rhubofix, caryophyllene oxide, linalool oxide,5-isoprophenyl-2-methyl-2-vinyltetrahydrofuran, nerol oxide, rose oxideand the like.

Examples of lactones include γ-undecalactone, 6-dodecalactone,γ-hexalactone, γ-nonalactone, γ-decalactone, γ-dodecalactone, jasminelactone, methyl γ-decalactone, γ-decenolactone, jasmolactone,propylidene phthalide, δ-hexalactone, δ-2-decenolactone,ε-dodecalactone, dihydrocoumarin, coumarin and the like.

Examples of the hydrocarbons include ocimene, limonene, α-phellandrene,terpinene, 3-carene, bisabolene, valencene, alloocimene, myrcene,farnesene, α-pinene, β-pinene, camphene, terpinolene, p-cymene, cedrene,β-caryophyllene, cadinene and the like.

Examples of the nitrogen-containing compounds or sulfur-containingcompounds include methyl anthranilate, ethyl anthranilate, methylN-methyl anthranilate, methyl N-2′-methylpentylidene anthranilate,ligantral, dodecanenitrile, 2-tridecenenitrile, geranylnitrile,citronellylnitrile, 3,7-dimethyl-2,6-nonadienonitrile, indole,5-methyl-3-heptanone oxime, limonene thiol, 1-p-menthene-8-thiol, butylanthranilate, cis-3-hexenyl anthranilate, phenylethyl anthranilate,cinnamyl anthranilate, dimethyl sulfide, 8-mercapto menthone and thelike.

Examples of the acids include acetic acid, propionic acid, butyric acid,valeric acid, hexanoic acid, octanoic acid, decanoic acid, dodecanoicacid, 2-decenoic acid, geranic acid, 2-methylbutyric acid,2-ethylbutyric acid, phenylacetic acid, cinnamic acid, isobutyric acid,isovaleric acid, 3-methylvaleric acid, 2-hexenoic acid,2-methyl-2-pentenoic acid, 2-methylheptanoic acid, myristic acid,stearic acid, lactic acid, pyruvic acid, cyclohexane carboxylic acid andthe like.

The synthetic aromachemical is commercially available or easilysynthesized as necessary. The material of natural origins is alsocommercially available or easily extracted and purified by a commonlyused method.

The content of the compound of the present invention represented by theformula (1) in the flavor or fragrance composition is suitablydetermined depending on the type or the application of flavor orfragrance composition and is generally preferably 1×10⁻⁸ to 50% byweight, more preferably 5×10⁻⁶ to 5% by weight, based on the totalweight of the flavor or fragrance composition, but is not particularlylimited thereto.

The flavor or fragrance composition of the present invention may furthercontain a carrier for flavor or fragrance. The carrier for flavor orfragrance which is used in the present invention may be a liquid carrieror a solid carrier.

Examples of the liquid carrier include water; lower alcohols such asethanol, propanol, isopropanol and butanol; glycerin; propylene glycol;triacetin and the like.

Examples of the solid carrier include natural gum substances such asArabic gum and Tragacanth gum, surfactants (for example, non-ionicsurfactants such as glycerin fatty acid ester and sucrose fatty acidester, anionic surfactants, cationic surfactant and amphiproticsurfactants), excipients (such as gelatin, dextrin), and anencapsulating agent (such as cyclodextrin).

The flavor or fragrance composition of the present invention may beprepared in the form of a stabilization or dispersion by solubilizing oremulsion-dispersing components in a solid carrier such as a natural gumand a surfactant. Alternatively, the flavor or fragrance composition ofthe present invention may be provided in the form of a powder coatedwith natural gums such as Arabic gum or excipients such as gelatin anddextrin, or may be microcapsulated by treating with a capsulating agent.Furthermore, the flavor or fragrance composition of the presentinvention can be stabilized and sustained-released by encapsulating withan encapsulating agent such as cyclodextrin.

In addition, the carrier for flavor or fragrance may be used alone or incombination thereof.

The flavor or fragrance composition of the present invention may furthercontain a flavor or fragrance retaining agent. Examples of the flavor orfragrance retaining agent used in the present invention include knownflavor or fragrance retaining agent materials used for the flavor orfragrance composition, such as glycerin, glyceride, dipropylene glycol,triethylcitrate, benzyl benzoate, benzyl salicylate anddiethylphthalate.

These flavor or fragrance retaining agents may be used alone or incombination thereof.

The flavor or fragrance composition of the present invention may furthercontain an antioxidant such as α-Tocopherol and BHT.

When fragrances and flavors are imparted to the various products usingthe flavor or fragrance composition of the present invention, the flavoror fragrance composition of the present invention used may be suitabledetermined depending on the type or final forms of products to whichfragrances and flavors are imparted (for example, product forms such asliquid, solid, powder, gel, mist and aerosol).

When fragrances and flavors are imparted to the various products usingthe flavor or fragrance composition of the present invention, the amountof the flavor or fragrance composition of the present invention used canbe adjusted depending on the type and form of various products andeffects or action required for products.

When the flavor composition is used for food products or beverages, thecontent of the compound represented by the formula (1) in the flavor orfragrance composition of the present invention is preferably adjusted to1×10⁻¹° to 0.01% by weight, more preferably 1×10⁻⁷ to 0.001% by weightbased on the total weight of the food products or beverages.

When the flavor or fragrance composition is used for fragrances orcosmetics, the content of the compound represented by the formula (1) inthe flavor or fragrance composition of the present invention ispreferably adjusted to 0.00001 to 0.3% by weight, more preferably 0.001to 0.05% by weight based on the total weight of the fragrances orcosmetics.

When the flavor or fragrance composition is used for daily necessitiesand household goods, the content of the compound represented by theformula (1) in the flavor or fragrance composition of the presentinvention is preferably adjusted to 0.00001 to 0.3% by weight, morepreferably 0.001 to 0.05% by weight based on the total weight of thedaily necessities and household goods.

When the flavor or fragrance composition is used for oral products, thecontent of the compound represented by the formula (1) in the flavor orfragrance composition of the present invention is preferably adjusted to1×10⁻⁷ to 0.001% by weight, more preferably 1×10⁻⁵ to 0.0001% by weightbased on the total weight of the oral products.

EXAMPLES

Hereinafter, the present invention will be described in detail withreference to the following examples, but the present invention is notlimited to these examples. In addition, apparatuses used for measurementof physical properties and the like in the following examples are asfollows.

NMR measurement apparatus: DRX 500 (Bruker Co., Ltd.)Gas chromatograph: GC 353B (GL Science)

Capillary column: TC-1 (15 m×0.53 mm)

Column temperature: 100→250° C. (elevation of temperature at 10° C./min)

Injection temperature: 250° C.

Detector temperature: 250° C.

Synthesis Flow of Example 1 to 6

Example 1 Synthesis of (7Z,10Z,13Z)-hexadecatrien-16-olide [formula (1);m=5, n=2] (A) Synthesis of Methyl 12-Hydroxydodeca-7,10-diynoate [(III);m=5]

23.00 g (0.22 mol) of 4-chloro-2-butyn-1-ol (I), 33.93 g (0.22 mol) ofmethyl 7-octynoate (II), 30.41 g (0.22 mol) of K₂CO₃, 32.98 g (0.22 mol)of NaI, and 20.95 g (0.11 mol) of CuI were added to 440 ml of DMF,followed by stirring at 30° C. for 48 hours. The reaction mixture wasquenched by adding to a saturated aqueous NH₄Cl solution (200 ml)(hereinafter, referred to as “sat. NH₄Cl aq.”), then the resultingmixture was extracted with ethyl acetate. The extract was washed withwater, concentrated, and the concentrate was purified over a silica gelcolumn (hexane/ethyl acetate=8/2 to 4/6 (volume ratio)) to obtain 30.97g of methyl 12-hydroxydodeca-7,10-diynoate having a GC purity of 93.3%(yield: 59.1% th). The structure thereof was confirmed by NMR.

¹H NMR (500 MHz, CDCl₃) δ ppm:

4.26 (2H, s), 3.68 (3H, s), 3.18 (2H, t, J=2.3 Hz), 2.33 (2H, t, J=7.5Hz), 2.15-2.19 (2H, m), 1.80 (1H, bs), 1.40-1.67 (6H, m).

(B) Synthesis of methyl 12-Bromododeca-7,10-diynoate [(IV); m=5]

30.97 g (0.139 mol) of methyl 12-hydroxydodeca-7,10-diynoate obtained in(A) and 69.31 g (0.209 mol) of carbon tetrabromide were added to 500 mlof dichloromethane. The solution was stirred under ice cooling and 54.82g (0.209 mol) of triphenyl phosphine was added thereto over one hour.After addition, the solution was stirred at room temperature for onehour to complete the reaction. The reaction mixture was concentratedunder reduce pressure, followed by filtering on a celite, and a cake waswashed with ether. The ether solution was concentrated, followed bypurifying on a silica gel column (hexane/ethyl acetate=9/1 to 6/4(volume ratio)) to obtain 30.08 g of methyl 12-bromododeca-7,10-diynoatehaving a GC purity of 94.2% (yield: 76.5% th). The structure thereof wasconfirmed by NMR.

¹H NMR (500 MHz, CDCl₃) δ ppm:

3.92 (2H, s), 3.67 (3H s), 3.20-3.23 (2H, m), 2.32 (2H, t, J=7.5 Hz),2.15-2.19 (2H, m), 1.36-1.67 (6H, m).

(C) Synthesis of methyl 16-hydroxyhexadeca-7,10,13-triynoate [formula(2); m=5, n=2, R=methyl]

30.08 g (purity of 94.2%, 0.105 mol) of methyl12-bromododeca-7,10-diynoate obtained in (B) above, 8.83 g (0.126 mol)of 3-butyn-1-ol (V), 14.51 g (0.105 mol) of K₂CO₃, 15.74 g (0.105 mol)of NaI, and 10.00 g (0.0525 mol) of CuI were added to DMF (200 ml),followed by stirring at 30° C. for 28 hours. The reaction mixture wasquenched by adding to sat. NH₄Cl aq. (80 ml), then the resulting mixturewas extracted with ethyl acetate, and the extract was washed with water.The organic layer was concentrated, followed by purifying on a silicagel column (hexane/ethyl acetate=7/3 to 4/6 (volume ratio)) to obtain21.70 g of methyl 16-hydroxyhexadeca-7,10,13-triynoate having a GCpurity of 95.3% (yield: 75.9% th). The structure thereof was confirmedby NMR.

¹H NMR (500 MHz, CDCl₃) δ ppm:

3.71 (2H, t, J=6.3 Hz), 3.67 (3H, s), 3.15-3.17 (2H, m), 3.12-3.14 (2H,m), 2.43-2.46 (2H, m), 2.32 (2H, t, J=7.6 Hz), 2.14-2.18 (2H, m), 1.85(1H, bs), 1.38-1.67 (6H, m).

(D) Synthesis of methyl 16-hydroxyhexadeca-(7Z,10Z,13Z)-trienoate[formula (3); m=5, n=2, R=methyl]

19.66 g (0.079 mol) of (CH₃COO)₂Ni.4H₂O was added to 1000 ml of 95%ethanol, 79 ml of a 1M NaBH₄ ethanol solution was further added theretoto prepare a Ni₂B ethanol suspension. 21.70 g (0.079 mol) of the methyl16-hydroxyhexadeca-7,10,13-triynoate obtained in (C) and 19.00 g (0.316mol) of ethylene diamine were added to 50 ml of ethanol, and theresulting solution was added to the above prepared Ni₂B ethanolsuspension, and hydrogenation was performed for one hour.

The catalyst was separated by filtration and the filtrate was dilutedwith isopropyl ether and washed with saturated brine. The residue wasconcentrated, followed by purifying on a column (hexane/ethylacetate=7/3 to 4/6 (volume ratio)) to obtain 14.73 g of methyl16-hydroxyhexadeca-(7Z,10Z,13Z)-trienoate having a GC purity of 96.1%(yield 67.0% th). The structure thereof was confirmed by NMR.

¹H NMR (500 MHz, CDCl₃) ppm

5.33-5.44 (6H, m), 3.67 (3H, s), 3.63-3.65 (2H, m), 2.79-2.86 (2H, m),2.29-2.39 (4H, m), 2.02-2.09 (2H, m), 1.66 (1H, bs), 1.58-1.65 (2H, m),1.29-1.40 (6H, m).

(E) Synthesis of (7Z,10Z,13Z)-Hexadecatrien-16-olide [formula (1); m=5,n=2]

14.72 g (52.5 mmol) of methyl 16-hydroxyhexadeca-(7Z,10Z,13Z)-trienoateobtained in (D) and 7.44 g (26.2 mmol) of titanium (IV) isopropoxide(Ti(i-PrO)₄) were added to 9000 ml of toluene, then the resultingmixture was refluxed for 8 hours. After cooling, the reaction mixturewas quenched by addition of water, organic layer was separated, andwashed with saturated brine. The resulting solution was concentrated,followed by purifying on a column (hexane/ethyl acetate=95/5(volumeratio)) to obtain 8.29 g of (7Z,10Z,13Z)-hexadecatrien-16-olide having aGC purity of 96.8% (yield 64.0% th). The structure thereof was confirmedby NMR.

¹H NMR (500 MHz, CDCl₃) δ ppm:

5.55-5.35 (6H, m), 4.16 (2H, t, J=5.9 Hz), 2.85 (2H, t, J=6.7 Hz), 2.81(2H, t, J=6.3 Hz), 2.38-2.41 (2H, m), 2.29 (2H, t, J=7.1 Hz), 2.04-2.08(2H, m), 1.62-1.67 (2H, m), 1.32-1.37 (4H, m).

Example 2 Synthesis of (6Z,9Z,12Z)-tetradecatrien-14-olide [formula (1);m=4, n=1]

(6Z,9Z,12Z)-Tetradecatrien-14-olide was synthesized in the same manneras in Example 1 except that methyl 6-heptynoate was used as a compoundof (II) and 2-propyn-1-ol was used as a compound of (V). The usedamounts (mol, equivalent, and time(s) content) were same as the case ofExample 1. The results of purity and NMR of products of respectiveprocesses are given as follows.

Methyl 14-hydroxytetradeca-6,9,12-triynoate [formula (2); m=4, n=1,R=methyl]

GC purity 96.7%

¹H NMR (500 MHz, CDCl₃) δ ppm:

4.26 (2H, s), 2.08 (3H, s), 3.20-3.21 (2H, m), 3.12-3.14 (2H, m),2.10-2.35 (1H, bs), 2.34 (2H, t, J=7.6 Hz), 2.17-2.21 (2H, m), 1.70-1.74(2H, m), 1.51-1.54 (2H, m).

Methyl 14-Hydroxytetradeca-(6Z,9Z,12Z)-trienoate [formula (3); m=4, n=1,R=methyl]

GC purity: 96.2%

¹H NMR (500 MHz, CDCl₃) δ ppm:

5.33-5.66 (6H, m), 4.19 (2H, m), 3.68 (3H, s), 2.77-2.88 (4H, m), 2.31(2H, t, J=7.5 Hz), 2.06-2.10 (2H, m), 2.02-2.05 (1H, bs), 1.36-1.43 (4H,m).

(6Z,9Z,12Z)-Tetradecatrien-14-olide [formula (1); m=4, n=1]

GC purity: 97.7%

¹H NMR (500 MHz, CDCl₃) δ ppm:

5.34-5.69 (6H, m), 4.61-4.63 (2H, m), 2.93-2.95 (2H, m), 2.80-2.82 (2H,m), 2.38-2.41 (2H, m), 1.99-2.04 (2H, m), 1.72-1.77 (2H, m), 1.36-1.42(2H, m).

Example 3 Synthesis of (6Z,9Z,12Z)-pentadecatrien-15-olide [formula (1);m=4, n=2]

(6Z,9Z,12Z)-Pentadecatrien-15-olide was synthesized in the same manneras in Example 1 except that methyl 6-heptynoate was used as a compoundof (II). The used amounts (mol, equivalent, and time(s) content) weresame as the case of Example 1. The results of purity and NMR of productsof respective processes are given as follows.

Methyl 15-hydroxypentadeca-6,9,12-triynoate [formula (2); m=4, n=2,R=methyl]

GC purity: 97.8%

¹H NMR (500 MHz, CDCl₃) δ ppm:

3.71 (2H, t, J=6.2 Hz), 3.68 (3H, s), 3.12-3.19 (4H, m), 2.43-2.46 (2H,m), 2.33 (2H, t, J=7.5 Hz), 2.17-2.21 (2H, m), 1.90-2.15 (1H, bs),1.69-1.75 (2H, m), 1.51-1.36 (2H, m).

Methyl 15-Hydroxypentadeca-(6Z,9Z,12Z)-trienoate [formula (3); m=4, n=2,R=methyl]

GC purity: 98.1%

¹H NMR (500 MHz, CDCl₃) δ ppm:

5.35-5.67 (6H, m), 3.67 (3H, s), 3.64-3.68 (2H, m), 2.80-2.87 (4H, m),2.30-2.39 (4H, m), 2.04-2.11 (2H, m), 2.04-2.11 (1H, bs), 1.36-1.43 (4H,m).

(6Z,9Z,12Z)-Pentadecatrien-15-olide [formula (1); m=4, n=2]

GC purity: 98.0%

¹H NMR (500 MHz, CDCl₃) δ ppm:

5.33-5.55 (6H, m), 4.16-4.19 (2H, m), 2.80-2.85 (2H, m), 2.37-2.42 (2H,m), 2.27-2.34 (2H, m), 2.04-2.10 (2H, m), 1.65-1.70 (2H, m), 1.32-1.44(4H, m).

Example 4 Synthesis of (7Z,10Z,13Z)-pentadecatrien-15-olide [formula(1); m=5, n=1]

(7Z,10Z,13Z)-Pentadecatrien-15-olide was synthesized in the same manneras in Example 1 except that 2-propyn-1-ol was used as a compound of (V).The used amounts (mol, equivalent, and time(s) content) were same as thecase of Example 1. The results of purity and NMR of products ofrespective processes are given as follows.

Methyl 15-hydroxypentadeca-7,10,13-triynoate [formula (2); m=5, n=1,R=methyl]

GC purity: 96.5%

¹H NMR (500 MHz, CDCl₃) δ ppm:

4.26 (2H, s), 3.67 (3H, s), 3.12-3.21 (4H, m), 2.33 (2H, t, J=7.6 Hz),2.31-2.34 (1H, bs), 2.15-2.19 (2H, m), 1.39-1.67 (6H, m).

Methyl 15-hydroxypentadeca-(7Z,10Z,13Z)-trienoate [formula (3); m=5,n=1, R=methyl]

GC purity: 95.3%

¹H NMR (500 MHz, CDCl₃) δ ppm:

5.33-5.55 (6H, m), 4.23-4.24 (2H, m), 2.07 (3H, s), 2.79-2.88 (4H, m),2.31 (2H, t, J=7.5 Hz), 2.04-2.09 (2H, m), 1.48-1.61 (1H, bs), 1.32-1.67(6H, m).

(7Z,10Z,13Z)-Pentadecatrien-15-olide [formula (1); m=5, n=1]

GC purity: 96.2%

¹H NMR (500 MHz, CDCl₃) δ ppm:

5.31-5.73 (6H, m), 4.54-4.59 (2H, m), 2.79-2.94 (2H, m), 2.30-2.38 (2H,m), 1.99-2.07 (2H, m), 1.61-1.70 (2H, m), 1.29-1.47 (6H, m).

Example 5 Synthesis of (5Z,8Z,11Z)-hexadecatrien-16-olide [formula (1);m=3, n=4]

(5Z,8Z,11Z)-Hexadecatrien-16-olide was synthesized in the same manner asin Example 1 except that methyl 5-hexynoate was used as a compound of(II) and 5-hexyn-1-ol was used as a compound of (V). The used amounts(mol, equivalent, and time(s) content) were same as the case ofExample 1. The results of purity and NMR of products of respectiveprocesses are given as follows.

Methyl 16-Hydroxyhexadeca-5,8,11-triynoate [formula (2); m=3, n=4,R=methyl]

GC purity: 91.9%

¹H NMR (500 MHz, CDCl₃) δ ppm:

3.66-3.70 (2H, m), 3.68 (3H, s), 3.12-3.14 (4H, m), 2.44 (2H, t, J=7.5Hz), 2.19-2.25 (4H, m), 1.78-1.85 (2H, m), 1.78-1.85 (1H, bs), 1.55-1.70(4H, m).

Methyl 16-Hydroxyhexadeca-(5Z,8Z,11Z)-trienoate [formula (3); m=3, n=4,R=methyl]

GC purity: 91.1%

¹H NMR (500 MHz, CDCl₃) δ ppm:

5.34-5.43 (6H, m), 3.67 (3H, s), 3.65 (2H, t, J=6.6 Hz), 2.79-2.82 (4H,m), 2.33 (2H, t, J=7.5 Hz), 2.06-2.14 (4H, m), 2.06-2.14 (1H, bs),1.67-1.74 (2H, m), 1.41-1.57 (4H, m).

(5Z,8Z,11Z)-Hexadecatrien-16-olide [formula (1); m=3, n=4]

GC purity: 96.9%

¹H NMR (500 MHz, CDCl₃) δ ppm:

4.12-4.17 (6H, m), 4.16 (2H, t, J=6.1 Hz), 2.79-2.82 (4H, m), 2.33-2.36(2H, m), 2.07-2.11 (4H, m), 1.68-1.73 (4H, m), 1.43-1.49 (4H, m).

Example 6 Synthesis of (6Z,9Z,12Z)-Hexadecatrien-16-olide [formula (1);m=4, n=3]

(6Z,9Z,12Z)-Hexadecatrien-16-olide was synthesized in the same manner asin Example 1 except that methyl 6-heptynoate was used as a compound of(II) and 4-Pentyn-1-ol was used as a compound of (V). The used amounts(mol, equivalent, and time(s) content) were same as the case ofExample 1. The results of purity and NMR of products of respectiveprocesses are given as follows.

Methyl 16-Hydroxyhexadeca-6,9,12-triynoate [formula (2); m=4, n=3,R=methyl]

GC purity: 95.4%

¹H NMR (500 MHz, CDCl₃) δ ppm:

3.75 (2H, t, J=6.2 Hz), 3.67 (3H, s), 3.13-3.14 (4H, m), 2.33 (2H, t,J=7.4 Hz), 2.28-2.31 (2H, m), 2.17-2.21 (2H, m), 1.65-1.90 (1H, bs),1.69-1.78 (4H, m), 1.51-1.56 (2H, m).

Methyl 16-Hydroxyhexadeca-(6Z,9Z,12Z)-trienoate [formula (3); m=4, n=3,R=methyl]

GC purity: 95.4%

¹H NMR (500 MHz, CDCl₃) δ ppm:

5.35-5.65 (6H, m), 3.67 (3H, s), 3.64-3.66 (2H, m), 2.80-2.83 (4H, m),2.31-2.34 (2H, m), 2.07-2.19 (4H, m), 2.07-2.19 (1H, bs), 1.62-1.68 (4H,m), 1.35-1.42 (2H, m).

(6Z,9Z,12Z)-Hexadecatrien-16-olide [formula (1); m=4, n=3]

GC purity: 96.1%

¹H NMR (500 MHz, CDCl₃) δ ppm:

5.32-5.47 (6H, m), 4.09-4.11 (2H, m), 2.81-2.84 (4H, m), 2.36 (2H, t,J=7.2 Hz), 2.04-2.21 (4H, m), 1.34-1.74 (6H, m).

Example 7 Sensory Evaluation

With respect to Z-form compounds represented by the formula (1) producedin

Examples 1 to 6, sensory evaluation of odor was performed byprofessional panelists. The results are shown in Table 1.

TABLE 1 Compound represented by the formula (1) m n Aroma note Exam-(7Z,10Z,13Z)- 5 2 Fruity and natural musky ple 1 Hexadecatrien-16-olidenote Exam- (6Z,9Z,12Z)- 4 1 Musky note with freshness ple 2Tetratadecatrien-14-olide and floral-like character Exam- (6Z,9Z,12Z)- 42 Unique musky note with ple 3 Pentadecatrien-15-olide elegantcreaminess (mositureness). Slightly animalic. Exam- (7Z,10Z,13Z)- 5 1Clear and impactive floral- ple 4 Pentadecatrien-15-olide musky note.Exam- (5Z,8Z,11Z)- 3 4 Musky note with soft ple 5 Hexadecatrien-16-olidecreaminess and fruitiness evocative of γ- undecalactone Exam-(6Z,9Z,12Z)- 4 3 Musky note with rich ple 6 Hexadecatrien-16-olidepowdery, creamy and animalic nuance

The compound represented by the formula (1) of the present invention hada unique musk aroma.

Example 8 Preparation of Fragrance Composition

A fruity/floral-type fragrance composition was prepared in accordancewith the prescription shown in Table 2

TABLE 2 wt % Apple-peach base 40 Dipropylene glycol 0.4 Ethyl methylphenyl glycidate 2 Hedione 10 β-Ionone 3 L-Citronellol 3 Linalool 18 8wt % DPG* solution of mercaptomenthone 0.2 Orange terpene 8γ-Undecalactone 5 Ethyl maltol 0.4 10 wt % DPG of solution(7Z,10Z,13Z)-hexadecatrien-16-olide 10 obtained in Example 1 Sum 100 *InTable 2, DPG represents dipropylene glycol.

Example 9 Preparation of Shampoo

A shampoo to which the fruity/floral-type fragrance composition obtainedin Example 8 was added at a ratio of 0.3% was prepared by a commonmethod. The prescription details are shown in Table 3. The obtainedshampoo suitably had a musk aroma.

TABLE 3 wt % Sodium lauryl polyoxyethylene ether sulfate 14 Amide propylbetaine laurate 4 Coconut fatty acid diethanolamide 3 Cationizedcellulose 0.5 Ethylene glycol distearate 1 Paraoxybenzoic acid ester0.25 Citric acid suitable amount Fragrance composition of Example 8 0.3Purfied water balance Sum 100

Example 10 Preparation of Conditioner

A conditioner to which the fruity/floral-type fragrance compositionobtained in Example 8 was added at a ratio of 0.3% was prepared by acommon method. The details of prescription are shown in Table 4. Theobtained conditioner suitably had a musk aroma.

TABLE 4 wt % Stearyl trimethyl ammonium chloride 0.5 Ammonium distearyldimethyl chloride 1.5 Jojoba oil 2.5 Cetanol 4.5 Liquid lanolin 2Polyoxyethylene stearyl ether 1.5 Concentrated glycerin 7 Paraoxybenzoicacid ester 0.25 Sodium hydroxide suitable amount Citric acid suitableamount Fragrance composition of Example 8 0.3 Purified water balance Sum100

Example 11 Preparation of Flavor or Fragrance Composition

A flavor composition was prepared in accordance with the prescription ofTable 5 below.

TABLE 5 Parts by weight Ethyl acetate 11 cis-3-Hexenol 3 Hexanol 5Benzaldehyde 2 Ethyl hexanoate 22 cis-3-Hexenyl acetate 2 Linalool 70Linalool oxide 4 Hexyl butyrate 25 Hexyl hexanoate 15 α-Terpineol 5Citral 15 cis-3-Hexenyl butyrate 4 cis-3-Hexenyl hexanoate 5 β-Ionone 6Ethyl butyrate 10 8-Mercapto menthone 0.01(6Z,9Z,12Z)-Tetradecatrien-14-olide obtained in Example 2 0.01 95%ethanol balance Sum 1000

Example 12 Preparation of Carbonated Drink

A carbonated drink (Brix 9.3, acidity: 0.13% (based on citric acid), pH3.4, gas volume: 3.0) was prepared using the flavor or fragrancecomposition prepared in Example 11 in accordance with the prescriptionshown in the following Table 6. In addition, a carbonated drink wasprepared as a control using the flavor composition prepared in the samemanner as in Example 11, except that (6Z,9Z,12Z)-tetradecatrien-14-olideobtained in Example 2 was not added.

The obtained carbonated drink had a remarkably highly fresh and naturalfruity note as compared to the control carbonated drink.

TABLE 6 Parts by weight Fructose glucose liquid sugar 93.9 Granulatedsugar 20.0 Anhydrous citric acid 1.3 Flavor or fragrance compositionprepared in Example 11 1.0 Sodium citrate 0.1 Water 200 Carbonated water783.7 Sum 1100

While the invention has been described in detail and with reference tospecific embodiments thereof, it will be apparent to one skilled in theart that various changes and modifications can be made therein withoutdeparting from the spirit and scope thereof.

This application is based on Japanese Patent Application No. 2011-040574filed on Feb. 25, 2011, the entire subject matter of which isincorporated herein by reference. In addition, all documents cited inthe specification are also incorporated herein by reference.

INDUSTRIAL APPLICABILITY

The compound of the present invention represented by the formula (1) hasa unique musk aroma such as fruit-like, floral-like, creamy-like andanimal-like aroma. The compound can impart the desired fragrances andflavors to various products such as food products or beverages,fragrances or cosmetics, daily necessities and household goods and oralproducts, and is thus useful.

In addition, by adding a small amount of the compound of the presentinvention represented by the formula (1) to various products, fragrancesand flavors such as naturalness, freshness and fruitiness can beimparted to the products.

The production method of the present invention is useful in that aZ-form of the compound represented by the formula (1) can be selectivelyproduced at a high purity.

1-8. (canceled)
 9. A ω-hydroxytriene esters represented by the followingformula (3):

wherein m represents an integer of 0 to 10; n represents an integer of 1to 11; and R represents a monovalent aromatic ring group having 6 to 20carbon atoms, or a monovalent hydrocarbon group having 1 to 20 carbonatoms which may have a substituent group, and a compound in which m is3, n is 2 and R is a methyl group is excluded, and each of wavy linesrepresents at least one of an E-configuration of C═C double bond and anZ-configuration of C═C double bond.
 10. The ω-hydroxytriene estersaccording to claim 9, wherein all of the wavy lines are theZ-configuration of C═C double bond. 11-13. (canceled)